There are a wide range of neurological and psychological disorders for which treatment may be provided by various means. For many disorders, administration of pharmaceutical agents is the most common treatment modality. In cases in which the symptoms of the disorder are resistant to pharmacological treatment or for which no pharmacological treatment exists, other modalities may be used, including neurostimulation.
Neurostimulation is a method of disease treatment which uses an electrical stimulator to provide a current signal which is used to stimulate the central nervous system (CNS), generally either directly or by means of a nerve of the peripheral nervous system. Such neurostimulators and their corresponding electrodes are generally implanted in a patient's body. There are currently two primary methods of neurostimulation for central nervous system disorders; deep brain stimulation (DBS) and vagus nerve stimulation (VNS). DBS uses an electrode implanted directly in a patient's brain, while VNS stimulates a patient's vagus nerve peripherally.
A commercially available DBS neurostimulator is manufactured and sold by Medtronic Inc. of Minneapolis, Minn., USA, model 3386, having a stimulating lead with four cylindrical stimulating electrodes. The deep brain stimulator is a surgically implanted medical device, similar to a cardiac pacemaker, which delivers high-frequency, pulsatile electrical stimulation to precisely targeted areas within the brain. The device consists of a very small electrode array (electrodes 1.5 mm in length with 3 mm center to center separation) placed in a deep brain structure and connected through an extension wire to an electrical pulse generator surgically implanted under the skin near the collarbone. The Medtronic DBS has received marketing clearance from the US Food and Drug Administration (FDA) with an indication for treatment of Parkinson's Disease, Essential Tremor, and Dystonia. Current research is evaluating DBS as a treatment for epilepsy, psychiatric disorders, and chronic pain.
The DBS stimulator is surgically placed under the skin of the chest of the patient. The stimulating DBS electrode lead is connected to the DBS stimulator wires and is placed in a specific inter-cranial location which may vary depending on the region of the brain being treated. The DBS system is adjusted by several parameters: 1. location of the 4 electrode lead, 2. selection of the stimulating electrodes, 3. amplitude of the stimulator signal, 4. frequency (repetition rate) of the stimulator signal, 5. polarity of the stimulating signal, and 6. pulse width of the stimulating signal. Post-implantation, all of these parameters except electrode location can be non-invasively varied by a clinician to enhance therapeutic effectiveness and minimize side effects. Amplitude, measured in volts, is the intensity or strength of the stimulation. The typical range is 1.5 to 9 volts. Frequency is the repetition rate at which the stimulation pulse is delivered and is measured in pulses per second (Hz); it typically ranges from 100-185 Hz. The pulse width is the duration of the stimulation pulse, measured in microseconds. The average pulse width ranges from 60-120 microseconds.
Another commercially available neurostimulator is designed for use on the peripheral nervous system, specifically the vagus nerve. An example of this type of system is designed and sold by Cyberonics Corporation. The Vagus Nerve Stimulator (VNS) Therapy device is implanted in a patient's chest under the skin immediately below the collarbone or close to the armpit. Two tiny wires from the device wrap around the vagus nerve on the left side of the neck. Through stimulation of this peripheral nerve, brain function is affected. VNS therapy has been granted marketing clearance by the FDA with an indication for treatment of epilepsy and is being investigated to treat a number of other central nervous system diseases and conditions, such as depression, obesity, Alzheimer's disease, etc.
An obstacle to the broader use of these devices is, in many indications, the lack of a measure of treatment efficacy. The efficacy of neurostimulation is a function of the settings of the various stimulator parameters (i.e., electrode selection, stimulus pulse amplitude, stimulus pulse frequency, stimulus polarity and stimulus pulse width, among others). However, with the exception of treatment for essential tremor or patients with very frequent epileptic seizures, it is difficult to assess the effect of the stimulus provided, and thus difficult to adjust these parameters to achieve the maximum possible treatment efficacy.
Prior Art
A number of different approaches have used the EEG as a feedback signal for neurostimulation.
In U.S. Pat. No. 6,263,237 issued to Rise, the use of a sensor in combination with a signal generator (neurostimulator) to treat an anxiety disorder is described. In this embodiment, the sensor generates a signal related to a condition resulting from the anxiety disorder. Control means responsive to the sensor signal regulate the signal generator so that the neurological disorder is treated. One of the types of sensor signals is cortical potentials recorded above the neurons controlling specific aspects of behavior associated with the neurological disorder; in this case, the sensor would take the form of an implanted depth electrode. In this system, the sensor is an integral component of the stimulating device. There is no teaching or suggestion in the patent, however, of the method of obtaining or computing a sensor signal relating to the anxiety disorder or to treatment efficacy.
In U.S. Pat. No. 6,066,163 issued to John, an Adaptive Brain Stimulation (ABS) system which aids in the rehabilitation of patients from traumatic brain injury, coma, or other brain dysfunction is described. The system comprises a sensor(s), a stimulating means, a comparator means for statistical comparison, and a means to adjust the stimulator according to the outcome of the comparison. The object of the system is to improve treatment of central nervous system pathology such as coma by relying on statistically significant and medically meaningful criteria to choose a specified program of stimulation. The John system specifically utilizes signals from the brain (EP and EEG), as well as EKG and EMG. John describes a large number of potential parameters that may be computed from these signals. The parameters are compared using statistical methods to a set of reference values from a database which may include values previously obtained from the patient, values that medical personnel have obtained, or values from an appropriate normative population. The ABS then selects a set of stimulation parameters based upon this comparison. A positive outcome is defined as the current state meeting a set of criteria indicating an improvement in the patient's condition. John describes the method only in a general sense; the patent does not teach any specific method or the use of any specific signals or parameters to quantify those signals, nor does it teach criteria which define positive outcomes. In addition, John does not teach the making of an index of treatment efficacy.
U.S. Pat. No. 6,539,263 issued to Schiff et al. describes a system for treating a conscious patient to improve cognitive function or coordination of function across a patient's cortical regions. Electrical stimulation is applied to at least a portion of the subcortical structures involved in the generation and control of generalized efference copy signals under conditions effective to improve the patient's cognitive function. Internally generated movement of the patient is then detected and in response to such internally generated movement, application of electrical stimulation is controlled. Schiff, et al. also state that their method can be optimized by monitoring regional and intrahemispheric changes in brain waves as measured by conventional techniques (EEG or magnetoencephalogram (MEG)) or by monitoring regional and intrahemispheric changes in metabolic activity. Schiff, et al., however, do not teach specific methods for processing the EEG or MEG signal to produce a parameter reflective of cognitive function.
U.S. Published Patent Application 2002/0013612A, filed by Whitehurst, describes a system for applying drugs and/or applying electrical stimulation to the brain to treat mood and/or anxiety disorders. The system described is fully implanted in the skull. In order to help determine the strength and/or duration of electrical stimulation and/or the amount and/or type(s) of stimulating drug(s) required to produce the desired effect, in one preferred embodiment, a patient's response to and/or need for treatment is sensed. Whitehurst states that the methods of determining the required electrical and/or drug stimulation include measuring the electrical activity of a neural population (e.g., EEG), measuring neurotransmitter levels and/or their associated breakdown product levels, measuring medication and/or other drug levels, hormone levels, and/or levels of any other bloodborne substance(s). He further states that the sensed information is preferably used to control the stimulation parameters of the System Control Unit(s) in a closed-loop manner. Whitehurst does not teach any method of processing the EEG signal to produce a parameter that can be used as a control variable, nor does he teach recording EEG from the surface of the head.
Others have examined EEG asymmetries (i.e., differences EEG metrics between brain hemispheres); “The common observation in electroencephalographic (EEG) studies of an altered pattern of asymmetric activation in anterior scalp regions in the reduced left relative to right activation in depressed or dysphoric individuals . . . ”.
A principal object of the present invention is to derive clinically meaningful information from the electroencephalogram signal to help optimize neurostimulation therapy.